1. Investigation of antibacterial mode of action of ω-aminoalkoxylxanthones by NMR-based metabolomics and molecular docking.
- Author
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de Oliveira PD, Martins ACF, da Silva Gomes R, Beatriz A, Alcantara GB, and Micheletti AC
- Subjects
- Microbial Sensitivity Tests, Molecular Docking Simulation, Xanthones pharmacology, Xanthones chemistry, Xanthones metabolism, Staphylococcus aureus drug effects, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents chemistry, Metabolomics methods, Magnetic Resonance Spectroscopy methods
- Abstract
Introduction: The knowledge of the mode of action of an antimicrobial is essential for drug development and helps to fight against bacterial resistance. Thus, it is crucial to use analytical techniques to study the mechanism of action of substances that have potential to act as antibacterial agents OBJECTIVE: To use NMR-based metabolomics combined with chemometrics and molecular docking to identify the metabolic responses of Staphylococcus aureus following exposure to commercial antibiotics and some synthesized ω-aminoalkoxylxanthones., Methods: Intracellular metabolites of S. aureus were extracted after treatment with four commercial antibiotics and three synthesized ω-aminoalkoxylxanthones. NMR spectra were obtained and
1 H NMR data was analyzed using both unsupervised and supervised algorithms (PCA and PLS-DA, respectively). Docking simulations on DNA topoisomerase IV protein were also performed for the ω-aminoalkoxylxanthones., Results: Through chemometric analysis, we distinguished between the control group and antibiotics with extracellular (ampicillin) and intracellular targets (kanamycin, tetracycline, and ciprofloxacin). We identified 21 metabolites, including important metabolites that differentiate the groups, such as betaine, acetamide, glutamate, lysine, alanine, isoleucine/leucine, acetate, threonine, proline, and ethanol. Regarding the xanthone-type derivatives (S6, S7 and S8), we observed a greater similarity between S7 and ciprofloxacin, which targets bacterial DNA replication. The molecular docking analysis showed high affinity of the ω-aminoalkoxylxanthones with the topoisomerase IV enzyme, as well as ciprofloxacin., Conclusion: NMR-based metabolomics has shown to be an effective technique to assess the metabolic profile of S. aureus after treatment with certain antimicrobial compounds, helping the investigation of their mechanism of action., Competing Interests: Declarations. Conflict of interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)- Published
- 2024
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